Cell adhesion molecules are surface proteins important for antigen sensitization and the migration of leukocytes to sites of inflammation. We are studying the expression of cell adhesion molecules in ocular inflammation, investigating the blocking of cell adhesion molecules as a treatment for uveitis and other ocular inflammatory diseases, and examining the effect of immunosuppressive agents on cell adhesion molecule expression in eyes with experimental autoimmune uveitis (EAU). We previously showed that intercellular adhesion molecule 1 (ICAM-1) is expressed in eyes with EAU before the infiltration of inflammatory cells. Further experiments showed that monoclonal antibodies against ICAM-1 and its counter-receptor lymphocyte function-associated antigen 1 (LFA-1) inhibit EAU development in mice. We demonstrated that cell adhesion molecules are important for both antigen sensitization and inflammatory cell infiltration into the eye, with additional sets of experiments showing the following: (1) that monoclonal antibodies against both ICAM-1 and LFA-1 will prevent inflammatory cell infiltration of the eye induced by endotoxin, and importantly that these antibodies can inhibit ocular inflammatory even when administered after signs of inflammation have been noted; and (2) that monoclonal antibodies against ICAM-1 and LFA-1 can inhibit in vitro proliferation of a uveitogenic cell line by interfering with the interaction between lymphocytes and antigen-presenting cells. These results suggest that cell adhesion molecules play an important role in the development of uveitis and that blockage of cell adhesion molecules may provide a new therapeutic approach for patients with inflammatory eye disease. Finally we examined the effect of immunosuppressive agents on the expression of cell adhesion molecules in animals with EAU. Ocular expression of cell adhesion molecules was delayed and downregulated in animals treated with corticosteroids and cyclosporine following immunization with retinal S-antigen. Downregulation of cell adhesion molecule expression may be one of the mechanisms by which immunosuppressive agents inhibit ocular inflammation.